The search for new medicines requires the discovery of new molecules, and the increasing awareness that saturated atoms correlate to successful drug development mandates that these molecules be three- dimensional. This increasing importance of saturated carbons in bioactive molecules provides exciting opportunities for the invention of new cross-coupling methods and new alkyl electrophiles from widely abundant starting materials. This research will focus on alkyl alcohols and amines for their unique and exciting potential as cross-coupling electrophiles. Alkyl amines and alcohols have traditionally been seen as synthetic targets, not substrates. However, their wide availability and the ease of their preparation in highly enantioenriched form makes them attractive alkyl electrophiles to address challenges in asymmetric synthesis and to identify new, previously untapped feedstocks for synthesis. Alkyl amines and alcohols can be prepared in high enantiopurity, making them ideal substrates for stereospecific cross-coupling reactions. Via carbon?oxygen (C?O) and carbon?nitrogen (C?N) bond cleavage of highly enantioenriched alcohol and amine derivatives, we will solve longstanding challenges in asymmetric synthesis. These stereospecific cross-couplings will advance these alcohol and amine intermediates into valuable, highly enantioenriched products, including those with traditionally challenging all-carbon quaternary stereocenters. Primary alkyl amines are found in molecules ranging from simple starting materials to drugs and biomolecules. Harnessing the ubiquitous amino (NH2) group, this research will develop chemistry to transform NH2 groups into a host of other functional groups via cleavage of the C?N bond. The ability to transform a C?N bond to a C?C (or C?X) bond offers powerful opportunities in late-stage functionalization of complex alkyl amines, derivatization of biomolecules, and early-stage synthesis. This goal will be accomplished via nickel- catalyzed cross couplings of redox-active Katritzky pyridinium salts, which are readily and selectively prepared from primary alkyl amines. The successful development of this chemistry will enable efficient access to three-dimensional molecules with potential bioactivity from widely available precursors. This research will also change the way chemists see and use these functional groups. The ultimate goal of this research is to invent cross-coupling methods for C(sp3)?X electrophiles that are as useful as those long-known for C(sp2)?X reagents for the discovery and synthesis of new medicines. By opening a new door for the synthesis of novel, drug-like molecules, this research will impact the discovery of new molecules with the potential to deepen our understanding of and ability to treat human disease.